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Turning Kids Into Grown-Ups. Parenting is fraught with uncertainty, changing with each generation. This hour, TED speakers share ideas about raising kids and how — despite our best efforts — we're probably still doing it wrong. Guests include former Stanford dean Julie Lythcott-Haims, former firefighter Caroline Paul, author Peggy Orenstein, psychologist Dr. Aala El-Khani, and poet Sarah Kay.
Parenting Doesn't Matter (Or Not As Much As You Think). The multibillion-pound parenting industry tells us we can all shape our children to be joyful, resilient and successful. But what if it’s all bunk? Intelligence Squared are bringing together a panel of top geneticists and parenting experts to explore just how important parenting is.Arguing in favour of the motion are Robert Plomin, Psychologist and Professor of Behavioural Genetics at the Institute of Psychiatry, Psychology and Neuroscience at King’s College London; and Stuart Ritchie, Lecturer in the Social Genetic and Developmental Psychiatry Centre at King’s College London.Arguing against the motion were Susan Pawlby, a developmental Clinical Psychologist with over 30 years of experience working with mothers and babies both in clinical and research contexts; and Ann Pleshette Murphy, a therapist, parenting counsellor and advocate for young children and their families.The debate was chaired by Xand van Tulleken, a medical doctor and broadcaster who has presented numerous shows for the BBC and Channel 4, often alongside his identical twin brother Chris. For information regarding your data privacy, visit acast.com/privacy
Positive psychology—with Martin Seligman. During the 1960s the field of psychology focussed on the science of how past trauma creates present symptoms, and how to reduce people’s misery. Professor Martin Seligman wanted to change that focus. He’s become known as the Father of Positive Psychology, and he’s had a profound influence worldwide. In Part 1 of our 2 programs with Martin Seligman, hear him address an exclusive audience in Australia on happiness and human flourishing.
How Journaling Can Make You 25% Happier (TPS154). Journaling is a bit of a buzzword in the productivity space, but with good reason. And in this episode, Mike and Brooks explain why it’s so important. They dive into the many benefits of journaling, and share 5 tips for making journaling actionable and effective. They explain how to implement a journaling habit, recommend some different tools and apps you can use, and explain how to make the habit stick. If you’ve never understood why you should journal or you have trouble doing it consistently, then this episode is for you.Get Podcast UpdatesDo you want to get an email with shownotes each time a podcast goes live? Then let us know where to send the updates by entering your first name and email. Cheat SheetWhy there’s a stigma associated with journaling (and why’s it isn’t true) [1:39]The benefits that come from pairing journaling and meditation [5:13]How journaling increases your mindfulness [7:53]The ways that journaling actually increases the likelihood that you will actually achieve your goals [9:55]How journaling strengthens self-discipline and improves communication skills [14:15]Why many people do something called “morning pages” and how it sets their day up for success [18:24]Why you don’t need to take a long time each day to journal (it’s the consistency that counts) [20:27]Why it is so important to keep your journal positive [24:09]The benefits of keeping a gratitude journal and how it impacts your outlook on your life [26:07]Why it is important to see the gains you’ve made by reviewing your journal [32:17]How to use journaling to identify pain points in your life so you can fix and solve them [36:38]AE recommendations for digital journals and apps you can use [38:38]Why you might want to use an analog journal and the benefits of pen and paper [48:42]Why it is so important for you to pick a time to journal that works for you and stick to it [55:03]Using automation and prompts to make journaling more efficient [58:24]5 tips to make the most of your journaling experience [1:04:56]Why you should review your journal on a regular basis [1:06:19]LinksSELF JournalTPS2: How to Get Started with JournalingTPS69: Journaling w/ Kendra WrightHow to Take Massive Action on Your Goals by Implementing the 12 Week Year Effectively (TPS138)The 12 Week Year: Get More Done in 12 Weeks than Others Do in 12 Months10% Happier by Dan HarrisHuffington Post “10 Surprising Benefits You’ll Get From Keeping a Journal”MoodnotesDay OneThe Five Minute JournalTextExpanderEvernoteLaunch Center ProJourney appBaron Fig notebooksField NotesMoleskineRhodia notebookBullet JournalMiracle MorningIf you enjoyed this episode, subscribe to the podcast on iTunes, Stitcher, Overcast, PocketCast or your favorite podcast player. It’s easy, you’ll get new episodes automatically, and it also helps the show gain exposure. You can also leave a review! Here’s how.
Rank #1: Iskandrian & Cantoni: Diagnostic performance of MPI with conventional and CZT-SPECT in detecting CAD. Listen to Ami Iskandrian and Valeria Cantoni discuss the recently published paper entitled ‘Diagnostic performance of myocardial perfusion imaging with conventional and CZT single-photon emission computed tomography in detecting coronary artery disease: A meta-analysis’.The authors of this article have provided a PowerPoint file which summarises the contents of the paper and is free for re-use at meetings and presentations: https://link.springer.com/article/10.1007/s12350-019-01747-3#SupplementaryMaterialThe article is available at: https://rdcu.be/bOx82Be sure to subscribe on your mobile device - search 'JNC/ASNC Podcast'.
Rank #2: Iskandrian & Scarabelli: Comprehensive review on cardio-oncology – Role of multimodality imaging. On April 26th 2016, Ami E. Iskandrian and Tiziano M. Scarabelli discussed Tiziano's review article entitled 'Comprehensive review on cardio-oncology: Role of multimodality imaging'.The authors of this article have provided a PowerPoint file which summarises the contents of the paper and is free for re-use at meetings and presentations: http://bit.ly/2BakB0fThe article is available at: http://rdcu.be/Hq1JA transcript of their interview can be found at: http://rdcu.be/Hq19Be sure to subscribe on your mobile device - search 'JNC/ASNC Podcast'.
Rank #1: Episode 29: ILLUMENATE US. C. Michael Gibson sits down with Sean Lyden to discuss the results.
Rank #2: Episode 71: ULTIMATE: A Randomized Trial of Intravascular Ultrasound Guidance. C. Michael Gibson and Junjie Zhang discuss ULTIMATE: A Randomized Trial of Intravascular Ultrasound Guidance of Coronary Drug-Eluting Stent Implantation in an All-Comers Patient Population.
Rank #1: The 2018 ACC/AHA Lipid Guidelines: A Little More or Less Canadian?. Dr. George Thanassoulis discusses the 2018 ACC/AHA Lipid Guidelines: A Little More or Less Canadian? in this May 2019 CJC podcast. CJC article: https://www.onlinecjc.ca/article/S0828-282X(19)30189-8/fulltext Guest Twitter handle: https://twitter.com/ThanassoulisMD
Rank #2: Cardiac Surgery in HIV Patients: State of the Art. Dr. Bobby Yanagawa discusses Cardiac Surgery in HIV Patients: State of the Art in this March 2019 CJC podcast. CJC article: https://www.onlinecjc.ca/article/S0828-282X(18)31280-7/fulltext Guest Twitter handle: https://twitter.com/BobbyYanagawa
Rank #1: ACCEL Lite: Featured ACCEL Interview With Michelle O'Donoghue and Mandeep Mehra. In this interview, Michelle O'Donoghue and Mandeep Mehra discuss the final analysis of the 1,028 patient cohort outcomes of MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3).
Rank #2: ACCEL Lite: Featured ACCEL Interview With Richard Conti and Athena Poppas. In this interview, Richard Conti and Athena Poppas discuss managing pregnancy in patients with valvular heart disease.
Rank #1: Episode 27: LBTs At TCT 2018 - How Will These LBTs Change My Practice?. Roxana Mehran discusses key takeaways from the TCT 2018 late breakers with C. Michael Gibson and Ajay Kirtane.
Rank #2: Episode 26: Late-Breaking Trials, Women in Cardiology, and the Best of TCT 2017. Today’s episode is hosted by Roxana Mehran and includes discussion on the TAVR field, new mitral data, and the best moments of TCT 2017.
Rank #1: ACC CardiaCast: The Cardio-Protective Nature of DM Pharmacotherapies. This podcast discusses the article "Lower Cardiovascular Risk Associated with SGLT-2i in >400,000 Patients: The CVD-REAL 2 Study." The multinational study explores real world evidence on the use of sodium-glucose cotransporter-2. As the incidence of type 2 diabetes mellitus rises in the United States, understanding the cardioprotective effects of new drug classes will prepare you to better treat your patients.
Rank #2: ACC CardiaCast: Optimal Lipid Therapy. In this podcast, Kim Birtcher, Seth Martin, Donald Lloyd-Jones, and Lynne Braun discuss what optimal lipid therapy and management look like in a post-ezetimibe world. They answer patient and colleague questions about lowering low-density lipoprotein (LDL) and debate if LDL can ever be too low. This is a rebroadcast from the clinical focus session at ACC.19.
Rank #1: Practice Made Perfect: Physician Compensation. In this episode, Cathleen Biga discusses the evolving trends in physician compensation and offers guidance on setting up compensation models.
Rank #2: Practice Made Perfect: Transforming Care in a Value Environment. In this episode, Cathleen Biga provides an overview of the current value environment of patient care and how to transition from fee for service to an alternative payment model, with a focus on Quality Payment Programs.
Rank #1: Sonography and Women’s Health. This issue of the Journal of Diagnostic Medical Sonography is dedicated to women’s health.
Rank #2: Understanding Sonography Clinical Decision-Making Learning Through Student Voices. Sonographers assume an important role in providing accurate diagnosis for prompt patient management. The manual task of scanning competency is driven by a high level of cognitive function in the form of clinical decision making (CDM). It is therefore critical that sonography students are grounded in the CDM fundamentals as part of their sonography education. The aim of this article is to seek better understanding of student views on CDM learning to inform educators of strategies to better support student learning. The first part of the article describes how CDM for sonography students is being developed at The University of Auckland. The second part of the article explores student perspectives of CDM learning and the application of CDM in the workplace. Using purposive sampling, five clinical supervisors and two students participated in semistructured interviews. Focus groups with students were conducted at the end of each semester, between July 2014 and June 2016. Thematic analysis was used to analyze and make sense of the data. Based on these qualitative findings, the authors make recommendations to advance CDM within the sonography curriculum.
Rank #1: Top Stories in Cardiology: July 2019. Topics this month range from chest-pain triage, to valsartan-related cancers, ischemia as a predictor of CV outcomes.
Rank #2: Top Stories in Cardiology: July 2018. NSAIDs plus NOACs, A Department of Justice investigation, the blood pressure of billions, defending CAC tests, TAVR reform, and more on Heart Sounds this month.
Rank #1: How a Snakebite and Sudden Death Led to Cardiology and Writing. A family history of sudden death was the impetus for author Sandeep Juahar's fascination with the heart, which led to a career in cardiology and his latest book Heart: A History.
Rank #2: Cardio Twitter: An Essential Tool for Staying Current. Drs Harrington and Yeh discuss the pros, cons, and cautions of using Twitter in the cardiovascular community.
Rank #1: Heart Rhythm August 2019/Dr.Chen. HeartRhythm Editor-in-Chief Peng-Sheng Chen, MD, FHRS summarizes the August 2019 issue of the journal.
Rank #2: Heart Rhythm January 2018/Dr.Chen. HeartRhythm Editor-in-Chief Peng-Sheng Chen, MD, FHRS summarizes the January 2018 issue of the journal.
Rank #1: Eagle's Eye View: Your Weekly CV Update From ACC.org (Week of August 5). This week's View, guest hosted by Dr. Deepak Bhatt, explores the incidence of sudden cardiac death among persons living with human immunodeficiency virus infection with heart failure, the effect of metformin on cardiovascular outcomes and all-cause mortality in patients with type 2 diabetes mellitus, the amputation-free survival and reintervention rates in patients treated with initial open surgical bypass or endovascular intervention for ischemic ulcers of the lower extremities, the impact of transcatheter tricuspid edge-to-edge valve repair (TTVR) of severe tricuspid regurgitation on kidney and liver functions, and the procedural and 1-year clinical and echocardiographic outcomes of patients treated with TTVR.
Rank #2: Eagle's Eye View: Your Weekly CV Update From ACC.org (Week of July 29). This week's View, guest hosted by Dr. Deepak Bhatt, explores the impact of prolonged spaceflight on orthostatic tolerance and blood pressure profile in astronauts, the prevalence of atrial fibrillation in former National Football League athletes compared with population-based controls, whether composite cardiovascular events are more prevalent in patients with rejected/abandoned proprotein convertase subtilisin kexin type 9 inhibitor prescriptions than in those whose prescriptions are paid, and if the plasma eicosapentaenoic acid abundance is associated with reduced hazard for primary heart failure events.
Rank #1: Circulation October 2, 2018 Issue. Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. FDG-PET CT was recently introduced as a new tool for the diagnosis of prosthetic valve endocarditis. However, can we improve on its diagnostic performance? Well, to learn more you have to listen to the upcoming featured discussion, right after these summaries. Our first original paper this week describes a potential novel therapy for hypertension. In this study from first author Dr Hu, corresponding author Dr Soong, from Yong Loo Lin School of Medicine National University of Singapore, authors showed that galectin-1 is a key regulator for proteasomal degradation of CaV 1.2 channels. L-type CaV 1.2 channels are known to play crucial roles in the regulation of blood pressure. In a series of elegant in vitro and in vivo experiments, the authors showed that galectin-1 promotes CaV 1.2 degradation by replacing CaV-beta and thereby, exposing specific glycines for polyubiquitination. This mechanistic understanding provided the basis for targeting CaV 1.2 galectin-1 interaction and demonstrated the modulatory role that galectin plays in regulating blood pressure. The study, therefore, offers a potential novel approach for the therapeutic management of hypertension. Direct oral anticoagulants or DOACs, are surpassing warfarin as the anticoagulant of choice for stroke prevention in non-valvular atrial fibrillation. However, DOACs outcomes in elective peri-procedural settings have not been well elucidated and remain a source of concern for clinicians. The next paper in today's issue was a meta-analysis designed to evaluate the peri-procedural safety and ethicacy of DOACs versus warfarin. For author Dr Nazha, corresponding author Dr Spyropoulos, from the Feinstein Institute for Medical Research in Northwell Health at Lenox Hill Hospital in New York, reviewed the literature for data from phase three randomized controlled trials comparing DOACs with warfarin in the peri-procedural period among patients with non-valvular atrial fibrillation. Sub study from four trials were included namely RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE-AF. The short-term safety and ethicacy of DOACs and warfarin were not different in patients with non-valvular atrial fibrillation peri-procedurally. Under an uninterrupted anticoagulation strategy, DOACs were associated with a 38% lower risk of major bleeds compared to warfarin. The next paper presents results from the Sarcomeric Human Cardiomyopathy Registry or SHARE, which combined longitudinal data sets curated by eight international hypertrophic cardiomyopathy specialty centers to provide a better understanding of the factors that contribute to heterogeneous outcomes in lifetime disease burden in patients with hypertrophic cardiomyopathy. First and corresponding author Dr Ho from Brigham and Women's Hospital and colleagues analyzed longitudinal clinical information on 4,591 patients with hypertrophic cardiomyopathy. By examining the data set spanning more than 24,000 patient-years, the mortality of patients with hypertrophic cardiomyopathy was shown to be 3-fold higher than the general population at similar ages. The lifetime cumulative morbidity of hypertrophic cardiomyopathy was considerable, particularly for patients diagnosed before age 40 years and patients with sarcomere mutations. Atrial fibrillation and heart failure were the dominant components of disease burden. Thus, young age of diagnosis and the presence of sarcomere mutations are powerful predictors of adverse outcomes in hypertrophic cardiomyopathy. These findings highlight the need for close surveillance throughout life and the need to develop disease-modifying therapies. The final original paper this week provides molecular insights into atherosclerosis and it shows that defective base excision repair of oxidative DNA damage in vascular smooth muscle cells promotes atherosclerosis. Now, we know that atherosclerotic blocks demonstrate extensive accumulation of oxidative DNA damage, predominantly as 8-oxoguanine lesions. In today's paper, first author Dr Shah, corresponding author Dr Bennett from University of Cambridge and colleagues studied levels of 8-oxoguanine and its regulatory enzymes in human atherosclerosis. They found that human plaque vascular smooth muscle cells showed defective nuclear 8-oxoguanine repair, associated with reduced acetylation of the base excision repair enzyme 8-oxoguanine-DNA-glycosylase-1. Furthermore, correcting the base excision repair defect in vascular smooth muscle cells alone markedly reduced plaque formation, thus indicating that endogenous levels of oxidative DNA damage in vascular smooth muscle cells promoted plaque development. And that brings us to the end of this week's summaries. Now for our feature discussion. Prosthetic valve endocarditis is a life-threatening complication. However, making a timely diagnosis of prosthetic valve endocarditis before the occurrence of severe complications is really difficult. Now, FDG-PET CT has recently been introduced as a new tool for the diagnosis of prosthetic valve endocarditis. However, previous studies reported only modest diagnostic accuracy and may have been hampered by confounders. But today's study, our feature study in Circulation, addresses this issue. We have none other than the corresponding author, Dr Ricardo Budde from Erasmus Medical Center in Rotterdam, the Netherlands, and our dear associate editor, Dr Victoria Delgado, who is in Leiden University Medical Center, also in the Netherlands. So please tell us, how does your study help us address this issue of the accuracy of FDG-PET CT Dr Ricardo Budde: What we actually did is that of course endocarditis is a relatively rare disease, so we had six hospitals in the Netherlands that collaborated on this study and in each of the hospitals we searched for PET CT scans that were performed in patients with a prosthetic heart valve, either because they were suspected of having endocarditis, or if they were meant for other purposes, for example oncological follow-up. Then we grouped all those CT scans together, interpreted the PET CTs anew by dedicated interpreters, and then compared the findings with the actual diagnosis in the patient, which of course is always difficult in endocarditis because to make the diagnosis is difficult. So, also, one year follow-up period was included in that to be absolutely certain whether the patient had endocarditis or not. By taking this whole cohort of patients, we were able to determine the diagnostic accuracy of PET CT, as well as by using a logistics model, identify confounders which influence the diagnostic accuracy of PET CT. I think the study that we did addresses several important aspects and the way it helps physicians in actually interpreting and implementing PET CT to diagnose endocarditis is two-fold. First of all, we identified confounders that have to be taken into account when interpreting and using the PET CT. For instance, low inflammatory activity at the time of imaging and the use of surgical adhesive during a prosthetic heart valve implantation are confounders which should be taken into account when interpreting the PET CT. Furthermore, the guidelines have always insisted on not to use or use it very cautiously PET CT within the first three months after prosthetic heart valve implantation. However, we showed that actually this period after implantation does not necessarily have to be taken into account as also a good diagnostic accuracy can be obtained within the first three months after implantation. Dr Carolyn Lam: Ricardo, that's wonderfully put. I don't do a CT, PET CT, routinely. In fact, I am echocardiologist and it used to be that infective endocarditis was diagnosed with echo. So Victoria, tell us, how does echo stand now with this information? Dr Victoria Delgado: That's a very good question but I think the guidelines set a very clear figure of how the diagnostic workup of patients with prosthetic valve endocarditis should be performed. An echocardiography is the first imaging technique. The point is that transthoracic echocardiography in patients with suspicion of prosthetic valve endocarditis is very challenging. In terms of ideal, echocardiography is probably the best imaging technique to do first to evaluate whether it is endocarditis or not. It's difficult, we have to take into account that for a specific prosthetic valve, particularly mechanical, the shadowing can make that we don't see the [inaudible 00:10:22] and sometimes it's difficult, particularly in the early phase immediately after implantation, all the inflammation can be confounder for presence of endocarditis. In those cases, I think that this study provides additional and important data highlighting which are the confounders when you use PET CT to evaluate depressions of endocarditis. I think that, when you take into account those confounders, the accuracy of this technique is very good in order to make or help in the diagnosis of these patients. So, echocardiography, I think that will remain as our first imaging technique to rule out [inaudible 00:11:10] we can see but in those cases where the diagnosis is not confirm or rule out with transthoracic and transesophageal echocardiography this study provides additional data and important data showing that PET CT is a valuable complementary imaging diagnostic test for these patients. Dr Carolyn Lam: Ricardo, would you agree with that because I think your study also emphasized that perhaps FDG-PET CT should be implemented early in the diagnostic workup to prevent the negative confounding effect of the low inflammatory activity? So how do we put this all together? Dr Ricardo Budde: Well actually, I agree with Dr Delgado that echocardiography is and should be the first-line test that you do if you have a patient that has a suspicion of endocarditis. I mean, the advantages of echocardiography are many and it's non-invasive, it's bedside-available if needed, it's patient-friendly, and it provides a huge amount of information so you should always start with echocardiography. However, sometimes it can be difficult by echocardiography, for the reasons just explained by Dr Delgado, and I think then PET CT should be considered. And when you want to do a PET CT, then you should do it early within the diagnostic workup. Actually, in the article, one of the figures is a flow chart which we provide, and it provides information on how we think PET CT can best be implemented in the workup of endocarditis. In this flow chart we also start with doing an echocardiography and also, importantly, consult the endocarditis time to make initial classification of whether it's a rejected, possible, or definite prosthetic heart valve endocarditis. After that, you can follow the flow chart and see when you can best implement PET CT, in our opinion. Dr Carolyn Lam: Indeed Ricardo, I am so glad you brought up this figure and listeners, you have to take a look at it. I can imagine that everybody will be using this and discussing it and how to incorporate this in the workflow. And indeed you do start with either transthoracic or transesophageal echo and blood cultures, so thank you for clarifying that. Now, for our clinicians out there, are there any situations you may be telling us to be a little more careful? Could you put it simply for us when it comes to the FDG-PET? Dr Ricardo Budde: You mean when not to perform a PET CT? Dr Carolyn Lam: Yeah, or when we have to be really careful about inaccuracies. Dr Ricardo Budde: I think, of course, the confounders that we indicate in the article, especially if bioglue has been used by the surgeon during the initial surgery. We know that bioglue can be seen on a PET CT as a false positive uptake of FDG and it's also important to note that this is a phenomenon that can persist for a very long time after a valve implantation. It could be for years, so especially that I think is a very important confounder to take into account and be careful when you interpret PET CT or use the PET CT and always read the original surgical report if it is available to obtain this information. Dr Carolyn Lam: That's wonderful advice. Victoria, do you have anything to add? Dr Victoria Delgado: No, I think that Dr Budde explained perfectly this figure that is key in the article and also how to evaluate patients with suspected endocarditis of prosthetic valve. One thing that sometimes we forget is starting from the first step that is a good clinical history which includes also a good evaluation of previous history and, if possible, what has been done in the patient. I think that this key information to understand the findings on the echocardiography, transthoracic or transesophageal, and the subsequent investigations that you are going to perform. Either CT which is considered, for example, when you have a definitive prosthetic valve endocarditis and you want to rule out potential complications such as abscess, for example, and if you perform a PET CT or other imaging modalities that then also indicate the presence of infection like, for example, [inaudible 00:15:26] leukocytes with PET, for example. Dr Carolyn Lam: And I just want to end up with one little point. Ricardo, how about the fact that part of your results don't corroborate the ESC guideline recommendations that they say you have to avoid FDG-PET in the recently implanted prosthetic valve. How do you feel it's going to play out for clinicians? Dr Ricardo Budde: Well, I think the 2015 ESC guidelines on endocarditis are a very important document. One must take into account that the inclusion of PET CT in the ESC guidelines was a major step, and some might say that it was a little premature to include the use of PET CT because the number of data that was out there were still relatively limited. I think it's something that we are learning along the way. Now that we are using PET CT more often we are more aware of what we do to findings that we get and also the findings that we have within specific timeframes after the implantation of a prosthetic heart valve. One of the things that I think is desperately needed also at the moment is to have a prospective study where we would do PET CT in patients after implantation of a prosthetic heart valve that do not show any signs of endocarditis where we do PET CT just to determine these normal uptake values. I think that would be a major contribution to the whole learning experience that we're currently having with implementing PET CT within prosthetic heart valve endocarditis. Dr Carolyn Lam: Indeed, and Ricardo your paper has added significantly to our understanding. Readers, remember, it's Figure 6 of our feature paper this week. It is a beautiful figure. Pick it up, take a look. In the meantime just thank you so much Ricardo and Victoria for joining me today. Listeners, don't forget to tune in again next week.
Rank #2: Circulation October 9, 2018 Issue. Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Sacubitril-valsartan reduces the risk of cardiovascular mortality among patients with heart failure with reduced ejection fraction. However, what are its effects on kidney function and cardiac biomarkers in people with moderate-to-severe chronic kidney disease? Well, stay tuned to find out, as we will be discussing the results of the UK Harp III Trial, right after these summaries. The first original paper this week reveals that inhibition of a long non-coding RNA may serve as a novel molecular therapy for aortic aneurysms. First author, Dr Li, corresponding author, Dr Maegdefessel from Technical University Munich, and colleagues, identified the long non-coding RNA H-19 with functional relevance in experimental aortic aneurysm progression in two mirroring models, a novel genetically mutated mini-pig model, as well as end-stage human disease. They found that H-19 mediated expression levels of the transcription factor hypoxia inducible factor 1-Alpha. Which, in the chronic hypoxic environment of an aneurysm, triggers apoptosis in aortic smooth muscle cells. This study, therefore, introduces inhibition of H-19 as a novel molecular therapy to limit smooth muscle cell death in progressing aortic aneurysms. The next study provides insights into molecular mechanisms underlying heart failure progression in chronic pressure overload. Co-first author, Dr Chiang and Alsina, co-corresponding authors, Dr Heck, from Utrecht University, and Dr Wehrens, from Baylor College of Medicine, and their colleagues developed a novel and unbiased way to comprehensively study protein phosphatase 1 or PP1 interactors in a mouse model of progressive heart failure induced by elevated afterload. This so-called PP1 interaction enabled simultaneous interrogation of multiple pathways relevant to heart failure pathogenesis. They found nine specific PP1 interactors that were strongly associated with heart failure progression. Among these, the PP1 regulatory subunit 7 was shown to play a central role by regulating the PP1 interaction, and by acting as a competitive molecular sponge of PP1. In clinical trials of direct oral anticoagulants for atrial fibrillation, patients with end stage kidney disease on dialysis were excluded. Today's study answers the question, "What are the outcomes with Apixaban in dialysis dependent end stage kidney disease patients with atrial fibrillation?" Co-corresponding authors Dr Siontis and Dr Saran from University of Michigan and their colleagues performed a retrospective cohort study of Medicare beneficiaries included in the United States Renal Data System from 2010-2015. All eligible patients were those with end stage kidney disease and atrial fibrillation undergoing dialysis who had initiated treatment with an oral anticoagulant. In prognostic score-matched analysis, Apixaban was associated with lower rates of major bleeding compared with Warfarin, whereas there was no difference in stroke or systemic embolism. Patients on standard dose of Apixaban of 5 mg had a lower rate of stroke and death compared to those on reduced dose Apixaban of 2.5mg. Thus, Apixaban may be associated with superior safety and comparable effectiveness outcomes as Warfarin in dialysis patients with atrial fibrillation. However, these findings require confirmation in a randomized trial setting. Does Canagliflozin have benefits in people with chronic kidney disease, including those with an Estimated Glomerular Filtration Rate, or EGFR, between 30 and 45, in whom the drug is currently not approved? First author Dr Neuen, corresponding author Dr Perkovic from the George Institute of Global Health, and their colleagues performed a secondary analysis of the CANVAS Program to describe outcomes in participants with and without chronic kidney disease, as well as according to baseline kidney function as measure by EGFR. They found that the effect of Canagliflozin on HbA1c was progressively attenuated at lower EGFR levels, but blood pressure and body weight reductions were comparable. The reduction in risk of major adverse cardiovascular events, hospitalization for heart failure and progression of kidney disease appeared similar across different levels of kidney function, down to an EGFR of 30. Safety outcomes were also mostly consistent, but the risk of hypoglycemia may increase as EGFR declines. That wraps it up for our summaries, now for our feature discussion. Cubitalis-valsartan improves outcomes in patients with heart failure with reduced ejection fraction, and we know that from the Paradigm trial, but what about its effects on kidney function and cardiac biomarkers in people with chronic kidney disease? Well, this week's feature paper provides important randomized trial data addressing this question. To discuss it, we have none other than the first and corresponding author, Dr Richard Haynes from University of Oxford, as well as our editorialist for the paper, Braden Manns and Matthew James, both from University of Calgary and in addition, we have Dr Justin Ezekowitz, associate editor who manages paper, and Justin is from University of Alberta. Welcome gentlemen, we have a full house. Richard, could you start by sharing about your trial and your findings? Dr Richard Haynes: So, the trial was called UK Harp-III, and it was really a pilot trial, just to work to investigate the effects of Cubitalis-valsartan on patients with chronic kidney disease, and in particular to see what it did for their kidney function in the short term, and also what it did to other measures of interest like their blood pressure and cardiac biomarkers. It was a randomized control trial double blind, among just over 400 people with chronic kidney disease, and we compared Cubitalis-valsartan with Irbesartan, which is standard of care for most of these patients. Our primary outcome was really to look at the effects of these drugs on kidney function when it was being precisely measured in hospitals. We found, actually, that Cubitalis-valsartan had very similar effects to Irbesartan on kidney function. So, there was no real difference in kidney function at any point in the trial between patients who were allocated the Cubitalis-valsartan or those allocated Irbesartan. Dr Carolyn Lam: Richard, the way you described it I'm sure you're prepared for this question so why Irbesartan as the control versus Valsartan? Dr Richard Haynes: That's a very good question and a question asked quite often. There were six of one and half a dozen of the other. We could have chosen Valsartan. The difficulty with that is that Valsartan doesn't have a license indication for the treatment of chronic kidney disease so if we found a difference people might have said we just chosen an inferior comparator, so we chose Irbesartan because that does have an indication for the treatment of proteinuria kidney disease and obviously that leaves us open for the question about how different Valsartan and Irbesartan are. My opinion is they might be subtly different, but I don't think the difference is big enough to really impact these results in any meaningful way. Dr Carolyn Lam: Indeed, and I know Braden and Matthew you have thought about it a lot. Congratulations on the beautiful editorial. I love the way you set the context in the heart failure world where perhaps we have noted something different with regards to kidney function. Would either of you like to start the ball rolling with discussing that? Matthew James: Sure, this is Matthew James. So really the Paradigm Heart Failure Trial is a very important place to start in thinking about the effect of these medications on kidney function. That was a very large trial that did report changes in estimated Glomerular Filtration Rate and did show a small but statistically significant change in kidney function between the Sacubitril-valsartan arm and the control arm. There are many potential mechanisms for that, but it is important to realize that there were limitations in the population specifically around chronic kidney disease due to the level of kidney function that the patients were enrolled in to the study. So, some of the patients with more advanced chronic kidney disease wouldn't have been included in the Paradigm Heart Failure Trial so this trial is actually giving us more information about patients with kidney disease who we would expect to be at higher risk of seeing progressive loss of kidney function or progression of their kidney disease. Dr Carolyn Lam: Thanks for setting that up and just to clarify for the audience here so in Paradigm EGFR went down to 30 right, and here in UK Harp we are talking about measured GFR down to 20. Am I right? Dr Richard Haynes: Eligibility was actually determined by the EGFR, the estimated GFR. Yeah it went down to 20, up to 60. We also had a much more proteinuria in the patients in Paradigm. Dr Carolyn Lam: Right, and do you have a take Richard on why the results seem different from at least the secondary analysis that Milton Packer wrote about on its effects on kidney function in Paradigm? Dr Richard Haynes: I do have a take. I'm really interested to hear what Braden and Matthew thought. My take was that probably when you've got heart failure one of the major determinants of how well your kidneys work is actually how well your heart is working. That is probably one of the major determinants in that setting and because we know Sacubitril-valsartan has such beneficial effects on cardiac function in people with heart failure perhaps it's not surprising that it then is protected by kidney function a little bit better than people given Enalapril in Paradigm. However, in UK Harp III, we had a group of patients whose kidney had very definite kidney disease and probably the determinants of kidney progression quite different and having any impact on their heart function probably wouldn't really be noticed because the effect of their kidney disease would outweigh that. Perhaps, Sacubitril-valsartan doesn't have any beneficial effects on the kidney itself. As far as we can tell, from what is a relatively small and a relatively short trial. Dr Carolyn Lam: Justin, I mean you come from the heart failure world too just like me. What was your take? Dr Justin Ezekowitz: I think there are a number of features here we should take a step back and think about. Number one is as Richard outlined there is a lot more proteinuria here than would typically be seen in a heart failure related population. So, the comparator between the two groups, while similar in overlap while co-manage these patients is somewhat different in terms of what the result we are looking for. So, you know, it brings to mind that what we look at in the secondary analysis in for example Paradigm, is simple EGFR creatinine changes versus here we are looking at a much more sophisticated measure of GFR plus also looking at a comparator that is known to reduce proteinuria and I would say stabilize or not change or prevent their progression of renal disease in the larger trials in the renal population. So, it's a slightly different population, a slightly different comparator as well. The importance in the choice of comparators becomes really important when we are looking for this specific effect. Now, to Richard's point, which he opened with, which is talking about this as a pilot project to a larger outcome trial, it is hard to know whether or not the effects that Richard and his team on the NT-proBNP, troponin, and other effects would play out in the larger cardiovascular outcomes trial that would be potentially different results than simply a GFR change or proteinuria change. I would be interested in Richard's thoughts on that and Matt and Braden's as well. Matthew James: Maybe we can also get add another question to Richard which this was a really well-done study and you talked about it being relatively small and certainly by heart standards this was a relatively small pilot study with a limited duration of follow up. By kidney standards, this is a fairly this would be a usual sized clinical trial and so getting all these patients in the trial was a wonderful result to start with and while the study wasn't directly looking at safety of these medications, there is some I think assurance we have some tolerability data at least with this medication and the challenge as Richard would well know in managing patients with chronic kidney disease once they developed more advanced chronic kidney disease GFR is less than 30 is often difficult to use medications because of side effects, high potassium, and things. The most challenging types of patients we see are patients with lower levels of kidney function and with low ejection fractions. So at least this paper provides some hope that we've got a medication that is reasonably well tolerated in that population. I think that when Richard talks about this being a pilot study where a lot of patients, in fact patients with chronic kidney disease are much more likely to die from heart disease than they are to develop end stage renal disease. For many types of patients that is true at least. So, we are often thinking about what medications could be used to improve cardiovascular outcomes. So, in that sense, again given that the majority of the structural heart disease is not necessarily reduced heart function but is left ventricular hypertrophy I'm sure, and perhaps Richard has some comments as to the next study that might be considered given this medication seemed tolerable. It didn't have the effects that were perhaps hoped on progression although in the Paradigm sub study there was only a difference of 0.5 ml per minute and they were powered to detect 3 ml per minute in this study but actually the immediate hemodynamic drop was about 3 ml per minute and then kidney function was relatively stable thereafter. So hard to imagine this study would have showed a difference in kidney function now in retrospect but potentially this opens up some additional studies to look at cardiovascular outcomes in patients with chronic kidney disease who don't have reduced ejection fraction. Dr Richard Haynes: I think that's a really good point. I think it would be fascinating to see the results of the Paradigm Trial with Sacubitril-valsartan in patients with heart failure and preserved ejection fraction. Nevertheless, I think this trial does raise the hypothesis that this might be a drug that could improve regardless of whether it has any effect on the kidney or not. It could be possibly be used for improving cardiac outcomes but I just don't think the trial that we've done is enough to justify that at the moment. I think it's a good indicator that it may well work, but I think before anybody could recommend that with much enthusiasm I think it would require a large outcomes trial but focusing quite rightly on cardiovascular outcomes in people with chronic kidney disease which as Matthew said is actually the major burden of disease in those patients. Dr Justin Ezekowitz I think the question remains though is if as a pilot trial at that time as a longer-term trial would there be any difference because the mechanism of action of Sacubitril is different from that of Irbesartan and that was also shown in the nice table you have in the supplemental file which talks about the Sacubrital lapse concentration going up with the lower GFR's. So, there is the potential for those small subgroups where the GFR is lower they may have a substantial benefit over a longer period of time, not measured necessarily by GFR but measured by clinical outcomes. I think that is where the balance of getting the pilot trial versus a longer follow-up clinical outcomes trial is really important to get. I may actually just state one other thing or two. First, it's really important to investigate or initiate a trial and this is one of critical parts of why we do clinical trials. Medicine tests the effects initially a pilot and then hopefully a larger trial. The second is the importance of randomization here. We all think that the shiny new medications are important but getting randomization in trials like this done are really advanced knowledge, so we know what to do with the medication if we are faced with it or if we want to make an important choice for a patient that we can really make a point for the patient that we will base it on the best scientific knowledge. The third point that I would just come back to something else that we have not talked about yet is this overall is a neutral trial. There are no major effects that were seen but the importance of getting a neutral trial done and published is really critical as this advances the field potentially, so others can now decide what to do and perhaps launch larger trials with cardiovascular outcomes or decide to do a different comparator or different other tasks forward. So, this one we emphasize it is critically important to get these types of trials done and then published. Dr Carolyn Lam: You know Justin, I couldn't have said it better and completely echo your words. We are so proud to be publishing your paper Richard and that beautiful editorial in circulation. So, I'm just going to wrap up then because in the absence of better data at the moment what is the main take home message of this trial for patients with CKD right now and their care providers. I would love to start with Braden because you wrote about it in the editorial as well. What do you think of the take home messages? Braden Manns: Well again I think that we often struggle when peoples GFRs are in the 20 to 30 range with identifying a medication that's tolerable particularly in the context of people with reduced ejection fraction. I must say personally I would now be comfortable using this medication in patients with reduced ejection fraction who remain symptomatic who have GFRs in the 20 to 30 range. Those patients aren't that common but feel comfortable now using that type of medication there despite the fact that most patients weren't necessarily enrolled in the Paradigm study. A much larger population though of patients with structural heart disease but not reduced ejection fraction who have chronic kidney disease. It is not clear to me where this medication fits in the armamentarium. As Justin says it certainly wouldn't use this in preference to an ace inhibitor or an angiotensin receptor blocker at this point. So, it's hard to know where it fits without some larger studies looking at cardiac outcomes. Matthew James: I agree with Braden. I think we are already seeing this medication now enter practice here in Canada. There is this overlap in population between the patients with kidney disease and impaired left ventricular ejection fraction, so this is actually very helpful for us when we see these patients in practice around the appropriateness of continuing these medications in this patient population. Dr Justin Ezekowitz: So, I think it's critically important to remember the take home message here is to do proper clinical trials and then do again the large trial because without that would not really advance in knowledge. There could be a huge value to a newer medication or potentially the old ones are still just as good as we if we continue them safely. Dr Richard Haynes: I'd like to echo what everybody said already really. I mean I think what Justin just said trial is the key. We can't get away from the need for randomized control trials. I'm pleased that we've managed to deliver this one. In terms of a clinical take home message I think if I was a patient with kidney disease and heart failure, especially with reduced ejection fraction, I hope that I would feel a bit more comfortable to take this drug now knowing is it going to benefit me from a cardiovascular point of view it doesn't seem it is going to do my kidneys any harm either. So, hopefully it will reassure more patients that they can yield the benefits of a trial this drug has. Dr Carolyn Lam: Great stuff! Thank you so much gentlemen. This has been such an enlightening conversation. Thank you very much to audience for joining us today. You've been listening to Circulation on the Run. Don't forget to tune in again next week.
Rank #1: Circulation: Arrhythmia and Electrophysiology July 2018 Issue. Paul Wang: Welcome to the monthly podcast On The Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor in chief, with some of the key highlights from this month's issue. In our first paper, Moo-Nyun Jin, Tae-Hoon Kim, and associates examined the 1-year serial changes in cognitive function, with or without atrial fibrillation catheter ablation. They used the Montreal cognitive assessment score in 308 patients undergoing atrial fibrillation ablation, the ablation group and 50 atrial fibrillation patients on medical therapy who met the same indication for atrial fibrillation ablation, the control group at baseline three months and 12 months. Cognitive impairment was defined as a published cutoff score of less than 23 points. Pre-ablation cognitive impairment was a detected in 18.5%. The Montreal cognitive assessment score significantly improved one year after radio frequency ablation. In both the overall ablation group, 24.9 to 26.4 p less than 0.001, and the propensity matched ablation group 25.4 to 26.5, but not in the control group. 25.4 to 24.8 p equals 0.012. Pre-ablation cognitive pyramid odds ratio 13.7, was independently associated with an improvement in one-year post ablation cognitive function. In our next paper, Zian Tseng, James Salazar and associates studied World Health Organization defined sudden cardiac deaths autopsied in the POstmortem Systemic InvesTigation of sudden cardiac death, the POST SCD study to determine whether premortem characteristics could identify autopsy defined sudden arrhythmic death among presumed sudden cardiac deaths. They prospectively identified 615 World Health Organization defined sudden cardiac deaths, of which 144 were witnessed. Autopsy defined sudden arrhythmic death had no extra cardiac or acute heart failure cause of death. Of the 615 presumed sudden critic deaths, 348 or 57% were autopsy defined, sudden arrhythmic deaths. For witness cases, using an emergency medical system model area under the receiver operator curve 0.75, included presenting rhythm of ventricular tech or cardiac fibrillation, pulseless electrical activity, while the comprehensive model, adding medical record data and depression, area under the curve 0.78. If only VTVF witness cases, 48 of those were classified as sudden arrhythmic death. The sensitivity was 0.46, and specificity 0.90. For unwitnessed cases, the emergency medical system model, area under the curve 0.68, included black race, male sex, age, time since last seen normal, while the comprehensive, area into the curve 0.75, added the use of beta blockers, antidepressants, QT prolonging drugs, opiates, illicit drugs and dyslipidemia. If only unwitnessed cases, less than one hour, n equals 59, were classified as sudden arrhythmic deaths, the sensitivities were 0.18, and specificity was 0.95. The authors concluded that models could identify pre-mortem characteristics to better specify autopsy defined sudden arrhythmic deaths, among presumed sudden cardiac arrests. The authors suggest that the World Health Organization definition can be improved by restricting witnessed sudden cardiac deaths to ventricular tachycardia fibrillation or non-pulseless electrical activity rhythms in unwitnessed cases to less than one hour since last normal, at a cost of sensitivity. In our next paper, Rafael Jaimes III and associates performed optical mapping of trends, membrane, voltage and pacing studies on isolated Langendorff-perfused rat hearts to assess the cardiac electrophysiology after mono-2-ethylhexyl phthalate, a phthalate with documented exposure in intensive care patients. The authors found that a 30-minute exposure to mono-2-ethylhexyl phthalate increased the atrioventricular node effector in period 147 milliseconds compared to 170 milliseconds in controls and increased the ventricular effective refractory periods of 117 milliseconds compared to 77.5 milliseconds in controls. Optical mapping revealed prolonged action potential duration at slower pacing cycle lengths. Mono-2-ethylhexyl phthalate exposure also slowed epicardial conduction velocity, 25 centimeters per second compared to 60 centimeters per second in controls. The authors concluded that acute mono-2-ethylhexyl phthalate exposure, at clinically relevant doses, has a significant effect on cardiac electrophysiology in the intact heart. Heightened clinical exposure to plasticized medical products may have cardiac safety implications and lead to cardiac arrhythmias. In our next paper, Stephan Willems and associates report the use of a novel, non-contact imaging and mapping system that uses ultrasound to reconstruct atrial chamber anatomy and measure timing and density of dipolar, ionic activation or charge density across the myocardium to guide ablation of atrial arrhythmias. They conducted a prospective non-randomized study, the UNCOVER AF trial which was conducted at 13 centers across Europe and Canada. In 127 patients with persistent atrial fibrillation who underwent mapping and catheter ablation, acute procedural efficacy of 98% was seen. At 12 months, the single procedure freedom from atrial fibrillation, on or off antiarrhythmic drugs, was 72.5%, with 23% undergoing retreatments following one or two procedures. Freedom from atrial fibrillation was 93.2%. The primary safety outcome was 98% was no device related major adverse events reported. In our next paper, Anne-Floor Quast, Niek Beurskens, and associates describe a novel, completely extracardiac pacing system, with a lead in the anterior mediastinum, outside the pericardium and circulatory system. A total of 166 or 95% out of 174 patients had a viable lead access path through the fourth, fifth, or sixth intercostal space. Access to the targeted implant location using delivery tool was successful in all five cadavers and three humans, without use of fluoroscopy, with an average lead delivery time of 121 seconds. No damage to the lung, pericardium, heart or internal thoracic vessels occurred. Pacing performance in six human subjects showed a voltage threshold of 4.7 volts in a threshold pulse width of 1.8 milliseconds. In our next paper, Yasuhiro Shirai and associates compare the ability to identify ventricular tachycardia isthmuses in ischemic and nonischemic cardiomyopathies. Of 445 patients, 228 with ischemic cardiomyopathy and 217 with nonischemic cardiomyopathy, undergoing VT ablation. Detailed entrainment mapping of at least one tolerated VT was performed in 111 patients, 71 with ischemic cardiomyopathy and 40 with nonischemic cardiomyopathy. Of 89 nonischemic cardiomyopathy VTs, the isthmus could be identified by endocardial entrainment in 55 or 62%, compared to only eight out of 47 or 17% nonischemic cardiomyopathy VTs, p less than 0.01. With combined endocardial and epicardial mapping, the isthmus could be identified in 56 or 63% ischemic cardiomyopathy VTs, and 12 or 26% of nonischemic cardiomyopathy VTs, p less than 0.01, while a similar proportion of patients any critical component, defined as entrance, isthmus or exit, could be identified in 85% of ischemic cardiomyopathy VTs and 79% of nonischemic cardiomyopathy VTs, p equals 0.3. Complete success, no inducible VT at the end of the procedure was 82% versus 65%, p equals 0.04 and a one-year single procedure VT survival, 82% versus 55%, p less than 0.01. Both higher in patients with ischemic cardiomyopathy. The authors concluded that among mappable ischemic cardiomyopathy VTs, critical circuit components can be usually identified on the endocardium. In contrast, among mappable nonischemic cardiomyopathy VTs, although some critical components can be typically identified with the addition of epicardial mapping, the isthmus is less commonly identified, possibly due to midmyocardial location. In our next paper, Miki Yokokawa and associates targeted documented but non-inducible clinical VTs, based on stored, implantable cardioverter defibrillator electrograms. Radio frequency ablation was performed in a consecutive group of 66 postinfarction VTs, in whom clinical VTs were non-inducible during an ablation procedure. In the first 33 patients, the control group, only inducible VTs were targeted. In the second 33 patients, non-inducible clinical VTs were targeted by pace mapping based on stored ICD-electrograms, the ICD electrogram guided ablation group. VT recurred in five patients or 15% in the ICD-electrogram guided approach, and in 13% or 39% in the control group. Freedom from recurrent VT was higher, p equals 0.04, in the ICD-electrogram-guided group, but there was no difference in ventricular fibrillation or total mortality between groups. In our next paper, Albert Feeny and associates examined whether machine learning could predict cardiac resynchronization therapy or CRT response. A training cohort was created from all Johns Hopkins patients and an equal number of randomly sampled Cleveland Clinic patients. All remaining patients comprise the testing cohort. Response was defined as greater than or equal to 10% increase in left ventricular ejection fraction. Machine learning models were developed to predict CRT response using different combinations of classification algorithms in clinical variable sets on the training cohort. 925 patients were included. On the training cohort, the best machine learning model was a naive Bayes classifier using nine variables, QRS morphology, QRS duration, New York Heart Association classification, left ventricular ejection fraction and end-diastolic diameter, sex, ischemic cardiomyopathy, atrial fibrillation, and epicardial LV lead. On the testing cohort, machine learning demonstrated better response prediction than guidelines, area under the curves 0.7 versus 0.65, p equals 0.012, and greater discrimination of event-free survival, concordance index 0.61 versus 0.56, p less than 0.001. The fourth quartile of machine learning model had greatest risk of reaching the composite endpoint, while the first quartile had the least, hazard ratio of 0.34, p less than 0.001. The authors found that machine learning with nine variables incrementally improved prediction of CRT response and survival beyond guidelines, but its performance with not improved by incorporating more variables. In our next paper, Bernhard Kaess, Charlotte Andersson and associates examine the familial clustering of cardiac conduction defects in the Framingham heart study, using multivariable-adjusted logistic regression models to investigate the association of parental AV block, complete bundle branch block, or a pacemaker insertion with occurrence of cardiac conduction abnormalities on offspring. Individuals with at least one effected parent with a conduction defect had at 1.65-fold odds for manifesting AV block, and 1.62-fold odds for developing complete bundle branch block. If at least one parent had any electrocardiographic conduction defect or pacemaker insertion, the offspring had 1.62-fold odds for experiencing any of these conditions. The Danish and nationwide administrative registries of nearly 3 million individuals and about five thousand incident pacemaker implantations, individuals with at least one first degree relative with a history of pacemaker insertion, had a multivariable-adjusted 1.68-fold incident rate ratio of undergoing pacemaker insertion. If the affected relative was less than or equal to 45 years of age, the incident rate ratio was markedly increased to 51.0. In our final paper, a review article, Venkat Nagarajan, Siew Ho Yen, and Sabine Ernst provide a detailed discussion of anatomic landmarks and considerations that will aid in his bundle pacing lead implantation. That's it for this month. We hope that you'll find the journal to be the go to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.
Rank #2: Circulation: Arrhythmia and Electrophysiology On the Beat December 2017. Paul Wang: Welcome to the monthly podcast On the Beat for Circulation, Arrhythmia, and Electrophysiology. I'm Dr. Paul Wang, Editor in Chief, with some of the key highlights from this month's issue. We'll also hear from Dr. Suraj Kapa, reporting on new research from the latest journal articles in the field. In our first study, Boris Schmidt and associates studied 134 patients with persistent atrial fibrillation, randomized to laser balloon or wide area circumferential pulmonary vein isolation using irrigated radiofrequency current ablation and 3D mapping. They found that 71% of patients in the laser balloon group had freedom from atrial fibrillation between 90 and 365 days after a single ablation, similar to 69% of patients in the radiofrequency group, p=0.40. In the laser balloon group, one patient developed stroke, one had false aneurysm and one had phrenic nerve palsy. In the radiofrequency group, two patients developed a false aneurysm and one patient needed surgical repair. Procedure and fluoroscopy times were similar between the two groups. The authors concluded that the two methods were associated with similar efficacy in patients with persistent atrial fibrillation. In the next study, Kairav Vakil and associates examined the success of VT ablation in elderly patients who were part of the International VT Center Collaborative Study Group Registry. Of the 2,049 patients in the registry, 33% or 681 were greater than or equal to 70 years of age with a mean age of 75 years. Compared to patients less than 70 years, patients 70 years or greater had higher in-hospital, 4.4% versus 2.3%, p=0.1 mortality, and also a higher one year mortality, 15% versus 11%, p=0.002. But they had a similar instance of VT recurrence, 26% versus 25% and a similar time to recurrence, 280 versus 289 days. The authors concluded that VT ablation in elderly is feasible with reasonable safety and modestly higher in-hospital and one year mortality with similar rates of VT recurrence at a one year compared to younger patients. In the next study, Angel Ferrero-de Loma-Osorio and associates studied the optimal dosage of cryotherapy using cryoballoon ablation of pulmonary veins. The study the prospective, randomized, multicenter, non-inferiority study including 140 patients with paroxysmal atrial fibrillation which was refractory to antirrhythmic drugs. Patients were randomly assigned to a conventional strategy group of 180 seconds cryoablation applications per vein with a bonus freeze 70 patients or a shorter time application protocol with one application that lasted the time required for a electrical time to effect plus 60 seconds and a 120 second freeze bonus, 70 patients. At one year followup there was no difference in freedom from atrial fibrillation 79.4% of the control group versus 78.3% in the study group, p=0.87. The time to effect was detected in 72% of the veins. The study and control group had similar mean number of applications per patient, 9.6 versus 9.9. compared to controls the study group had a significantly shorter cryotherapy time, 28.3 versus 19.4 minutes, p80 or >90, especially when one refers to the appropriate use criteria where appropriateness was reclassified based on what the age range was and what the indication was from a primary prevention defibrillator. Further study is need to understand whether we really should apply an age cutoff to the benefit of ICDs but it is an important thing to consider when counseling patients, especially in light of evolving evidence in this area. Still staying in the realm of heart failure but now going to more basic electrophysiology, we review a paper published in Circulation this past month by Cho et al., entitled Delayed Repolarization Underlies Ventricular Arrhythmias in Rats With Heart Failure and Preserved Ejection Fraction. Increasingly, heart failure with preserved ejection fraction is being diagnosed to the point where it is now approximately half of all diagnosed heart failure with incidences that continue to increase nevertheless. One of the leading causes of mortality in heart failure with preserved ejection fraction is sudden death but the underlying mechanisms for this is less clear. Thus in a rat model, Cho et al., sought to evaluate why heart failure with preserved ejection fraction might result in an increase risk of sudden death. They exposed salt sensitive rats to a high salt diet and evaluated the effect on systolic and diastolic function. After verifying, some rats that suffered from HFpEF at this point versus control rats, they underwent programmed electrical stimulation and they measured corrected QT interval from surface ECG as well. Furthermore they did optical mapping, whole-cell patch clamping and quantitative polymerase chain reaction and Western blotting to evaluate ion channel expression. They noted that 31 of 38 rats exposed to a high salt diet demonstrated diastolic dysfunction and preserved ejection fraction along with signs of heart failure. There was an increased susceptibility to ventricular arrhythmias amongst these particular rats when compared to controls. They also noted that the corrected QT interval was significantly longer. Interestingly optical mapping showed that these rats had prolonged action potentials and multiple reentry circuits during induced ventricular arrhythmias. Furthermore there was confirmed a delay of repolarization based on patch clamping with a downregulation of transient outward potassium currents or ITO. Finally they noted that there was a downregulation of IK1 as well as IKR. Thus they felt that the susceptibility to ventricular arrhythmias was indeed markedly increased, at least in a rat model of HFpEF. These could be caused by QT prolongation, which is associated with delayed repolarization from downregulation of potassium currents and also associated multiple reentry circuits which can mediate ventricular arrhythmia. These findings are significant in that they highlight both potential targets for sudden death risk in the setting of HFpEF as well as potential targets for treatments that might prevent ventricular arrhythmias in the long term. Staying within the realm of ventricular arrhythmias, we next review an article by Do et al., published in the Journal of the American Heart Association this past month, entitled Thoracic Epidural Anesthesia Can Be Effective for the Short‐Term Management of Ventricular Tachycardia Storm. Similar to the earlier discussed article, of optogenetic stimulation of left stellate ganglion, even short term management options for VT storm are important. Some inject lidocaine or bupivacaine into the left stellate ganglion or into both stellate ganglia in order to get control. However, depending on comfort level, the utility of this may be variable at different institutions. Thus, novel therapies aimed at modulating the autonomic nervous system that might be available at other institutions such as thoracic epidural anesthesia are important to consider. The group sought to evaluate via multicenter experience what the effect on VT storm was with thoracic epidural anesthesia. They noted amongst 11 patients reviewed between July 2005 and March 2016 that the majority who underwent thoracic epidural anesthesia had incessant VT with a minority of them being polymorphic VT. Furthermore almost half of them had nonischemic cardiomyopathies. Almost half of the patients had a complete response to thoracic epidural anesthesia where the VT became quiescent. And one patient had a partial response. Thus, they suggested that thoracic epidural anesthesia may be effective and should be considered as a therapeutic option in patients with VT storm, especially those with incessant VT, who are refractory to initial management. They also noted clinically that improvement in VT burden associated with deep sedation may suggest a higher likelihood of responding to thoracic epidural anesthesia. For a clinical electrophysiologist especially in community hospitals where rapid utilization of ablation may not be possible or other advanced methods of autonomic modulation might not be feasible, options such as thoracic epidural anesthesia are important to be considered. They exist in an armament that includes intravenous drugs, left stellate ganglion injections, general anesthesia and use of IV beta blockers. These findings are highly suggestive and the fact that certain clinical characteristics might suggest those that are more likely to benefit might just to clinicians exposed to a patient of VT storm what the next step should be. Changing gears a little bit we will now review an article by Rafaat in the Journal of the American Heart Association entitled Swine Atrioventricular Node Ablation Using Stereotactic Radiosurgery: Methods and In Vivo Feasibility Investigation for Catheter‐Free Ablation of Cardiac Arrhythmias. The group sought to demonstrate using a linear accelerator based stereotactic radiosurgery system whether or not atrioventricular node ablation could be safely performed with minimal damage to surrounding structures. They used the linear accelerator to apply energy in a pig model after implantation of a pacemaker using a CT scan to guide therapy. They also performed pathologic evaluation of the region of the AV node and the surrounding tissues. They found that all animals included had disturbances of AV conduction with progressive transition into complete heart block. There was no damage to the surrounding myocardium and all pigs had preserved systolic function echocardiography. Thus they suggested that catheter free radioablation using this approach might be feasible in an intact swine. These findings are important because they build on other studies done by groups at other centers suggesting that noninvasive linear accelerator based therapies either using stereotactic radiosurgery with existing technologies, proton beams, carbon beams or other approaches, might offer feasible methodologies for noninvasive treatment for cardiac arrhythmias. Further study is indeed needed to validate what the effect on surrounding tissues actually is. Next we will review an article published by Williamson et al., in JACC Clinical Electrophysiology this past month entitled Real-World Evaluation of Magnetic Resonance Imaging in Patients With a Magnetic Resonance Imaging Conditional Pacemaker System. Results of four year prospective followup in over 2,600 patients, while MRI conditional pacemakers are more increasingly used, long term longevity as well as effects of multiple MRI scans in terms of MRI functioning the devices is unclear. Thus, the study was sought to be a large scale, real world evaluation of MRI in patients with MRI conditional pacemakers. They included over 2,600 patients in multiple centers and all these patients had a SureScan pacing system. They noted that there were no MRI related complications occurring during or after the MRI, meeting the primary objective. In fact, almost a third of the patients underwent two or more scans and even then there was no cumulative increase in problems in these patients. The pacing capture thresholds stayed stable throughout all patients. Thus this report constituted the largest longitudinal MRI experience in patients implanted with an MRI conditional device. The importance of this is to be able to highlight to patients that in fact even multiple MRIs despite having a device in place is safe. There is an increasing body of data that suggests that however, MRIs might be safe in a controlled setting, even in patients with legacy pacemakers. Whether MR conditional pacemakers actually offer incremental safety over legacy pacemakers however, is less clear and will likely require randomized trials of a large scale given the low number of events to really come to a conclusion. However, in most centers where it's not possible to do MRIs in legacy pacemakers, this offers some level of certainty that patients will likely be safe even undergoing multiple MRIs in a setting of having chronic pacemakers that are MRI conditionally safe. Staying within the realm of looking at large multicenter experiences, we review an article by Hosseini et al., entitled Catheter Ablation for Cardiac Arrhythmias, Utilization and In-Hospital Complications, 2000 to 2013, published in JACC Clinical Electrophysiology this past month. In this study, Hosseini et al., sought to investigate the overall utilization and in-hospital complications associated with catheter ablation in of all types in the United States between 2000 and 2013 using the National Inpatient Sample and Nationwide Inpatient Samples. They included all patients 18 years of age and older who underwent inpatient catheter ablation over this time period. They estimated total a total of almost 520,000 inpatient ablations performed in this time period with a median age of 62 years amongst patients. Interestingly the annual volume of ablations and the number of hospitals performing ablations increased year over year but the rate of complications and length of stay also increased. A large number, almost more than a quarter of inpatient ablation procedures were actually performed in low volume hospitals and in turn were associated with an increased risk for complications with an odds ratio 1.26. Independent predictors of in-hospital complications and in-hospital mortality included complex ablations for atrial fibrillation and ventricular tachycardia, older age and a greater number of comorbidities. In addition to this, lower hospital volumes was an independent predictor of complications. Thus the authors note that there has been a steady progressive in the number of in-hospital catheter ablation procedures. However, despite the increasing number, the number of periprocedural complications is increasing which may be partly mediated by taking in sicker patients from a complex procedures but also to performing these at lower volume centers. These findings are critical when considering the future of ablation strategies and ablation performance when we consider multicenter experiences or when we consider where certain procedures might be performed based on the experience of the operator or the institution. Why exactly it is that lower volume centers of higher complication rates still needs to be evaluated. However, it should be understood that ablations are complex procedures and thus require a certain amount of experience in order to allow for procedural efficacy and safety similar to any cardiac surgery or other procedure. It remains to be understood what the number of procedures to be able to be felt to be competent and safe should be. But, these findings should be considered by all providers based on their own personal experience and based their own personal numbers. Staying with the realm of catheter ablation, we will next review an article by Haldar et al., published regarding Catheter ablation vs electrophysiologically guided thoracoscopic surgical ablation in longstanding persistent atrial fibrillation: The CASA-AF Study in last month's edition of Heart Rhythm. In this article, they sought to evaluate catheter ablation outcomes for longstanding persistent atrial fibrillation as compared with those of thoracoscopic surgical ablation. There's a limited amount of data comparing these two methodologies for ablation. They included 51 patients with de novo symptomatic atrial fibrillation. 26 underwent thoracoscopic surgical ablation and the remainder underwent stepwise left atrial ablation with a primary end point being single-procedure freedom from atrial fibrillation and atrial tachycardia lasting >30 seconds without antiarrhythmic drugs at 12 months. They noted that single- and multi procedure freedom from atrial fibrillation was higher in the surgical ablation group than in the catheter ablation group. Namely the overall success rate from the surgical ablation group was 73% versus 32% in the catheter ablation group. It should be noted that there was testing of the surgical ablation lesion set by electrophysiologists that was felt increased success rate in achieving acute conduction block by 19%. It also should be noted that the complication rate in the surgical ablation group, was significantly higher than the catheter ablation group, namely 27% versus 8%. This did not reach statistical significance however, possibly due to the low numbers considered. The conclusion from the authors was that meticulous electrophysiologically guided thoracoscopic surgical ablation as a first line strategy in long standing persistent atrial fibrillation, may provide excellent single procedure success rates as compared with traditional catheter ablation. However again, there is an increased upfront risk of nonfatal complications. These considerations are important when thinking about what strategy to use in specific patients. Whether at a large level, thoracoscopic surgical ablation should be routinely used is still unclear and larger studies are likely needed to compare different modalities of ablation to better evaluate which is the right one for which patients. Again staying in Heart Rhythm in 2017, we next review an article by Sheldon et al., published regarding Catheter ablation in patients with pleomorphic, idiopathic, premature ventricular complexes. When a patient presents with idiopathic PVCs that are a single monomorphic focus, it is often considered reasonable to ablate them. However when patients have pleomorphic PVCs or polymorphic PVCs, the role of ablation is less clear and often considered more complex. Thus in this study, Sheldon et al., sought to evaluate patients who underwent ablation with pleomorphic PVCs. They reviewed about 100 consecutive patients 31% of whom had pleomorphic versus 69% who had monomorphic PVCs, however all of who were considered idiopathic. They noted the overall success rate was lower in patients with pleomorphic PVCs, namely 71% versus 90%. In fact, the presence of pleomorphic PVCs was independently associated with unsuccessful ablation. Also, pleomorphic PVCs more often had an epicardial origin than did monomorphic PVCs. And repeat ablation procedures were required in almost 20% of the cohort. Interestingly, three of the patients who came back for another procedure, had an increase of a nonpredominant PVC and one patient had a newly emerged PVC focus. The conclusion by Sheldon et al. Was the presence of pleomorphic PVCs can affect ablation outcomes but it's still possible to achieve successful elimination of the predominant PVC even if not all PVCs are targeted. Furthermore, they suggested that most recurrences are due to reemergence of the originally targeted predominant PVC morphology though sometimes other PVC morphologies may arise. Larger scale evaluation is still necessary to understand when a patient should be taken to ablation and when not. We recognize that sometimes the presumption of idiopathic might be due to a lack of consideration of other ideologies such as subclinical inflammation that can be related to myocarditis or sarcoidosis or other finding. Thus it should always be considered what the actual underlying substrate is with rigorous imaging such as MRI or PET scanning. However, the findings by Sheldon et al. suggest that just because there are multiple PVC morphologies present, does not necessarily mean that they cannot be ablated. Switching gears away from PVCs, we next review an article by Romero et al. published in Heart Rhythm this past month entitled Emergence of atrioventricular nodal reentry tachycardia after surgical or catheter ablation for atrial fibrillation: Are we creating the arrhythmia substrate? They reviewed patients who had AVNRT ablation performed and sought to evaluate how many of them had prior surgical or catheter ablation for atrial fibrillation. They reviewed cases of ablation for specifically persistent atrial fibrillation who eventually required a repeat ablation procedure and had a diagnosis of AVNRT at that time. A total of nine patients were identified meeting these characteristics. All of these patients were noted to have evidence of atrial fibrosis in the septum or proximal CS, and in fact six had undergone ablation either at the septum or the coronary sinus ostium or body and the other three had inferior mitral lines at a surgical MAZE approach. All had typical AVNRT inducible that was abolished with slow pathway ablation, though five required ablation in the roof of the coronary sinus or on the mitral valve annulus. Thus Romero et al. concluded that ablation involving the septum or proximal CS may create a substrate that can induce AVNRT. These findings are important when we consider ablation. Oftentimes when we do ablation, we think of a targeting substrate without thinking about the substrate we might create. Thus, rigorous evaluation for other mechanisms of tachycardia that one might not think of because of the absence of it during the index ablation should always be considered such as the creation of substrate for AVNRT. While most of us will consider atrial flutters or focal atrial tachycardias or macro reentry atrial tachycardias as the principle mechanisms of tachycardia in patients returning after prior atrial fibrillation ablation should also be considered that we might be creating substrate for other types of arrhythmias such as AVNRT. The next article we will review is published in the American Journal of Physiology, Heart and Circulatory Physiology by Yang et al., entitled Effect of ovariectomy on intracellular calcium regulation in guinea pig cardiomyocytes. It is believed that long-term deficiency of ovarian hormones after ovariectomy can alter cellular calcium handling mechanisms in the heart that can in turn result in the formation of a proarrhythmic substrates. This is important when considering possible arrhythmogenic mechanisms in women who might be undergoing ovariectomy or who might be in a post menopausal state. Thus in a series of animals, they evaluated the effective of ovariectomy as well as estrogen supplementation to ovariectomized animals on calcium handling at the level of the heart. They demonstrated that the ovariectomized guinea pig cardiac myocytes had higher frequencies of calcium waves and isoprenaline challenged cells displayed more early after depolarizations after ovariectomy. In addition to this, they noted the observations of calcium regulation alternations were not observed in myocytes from ovariectomized guinea pigs who were supplemented with 17β-Estradiol suggesting that in fact, these changes in the arrhythmogenic substrate were due to ovarian hormone deficiency resulting in dysregulation of cardiac calcium. While this was all performed at the level of guinea pigs, it is an important consideration again, as a potential mechanisms of cardiac arrhythmogenesis in women who might be undergoing ovariectomy or who might be post menopausal. In some cases ovarian hormones might be beneficial in regulating the arrhythmogenic substrate. The next article we review is published in Heart this past month by Stewart et al., entitled Nitric oxide synthase inhibition restores orthostatic tolerance in young vasovagal syncope patients. Syncope is probably one of the most difficult things that we treat in electrophysiology. In particular, vasovagal syncope. People have looked at different pacing maneuvers and specialized pacemakers for treatments. However, there's improving body of knowledge regarding other mechanisms, specific physiologic mechanisms that might underlie vasovagal syncope. This group in question had previously demonstrated that impaired post synaptic adrenergic responsiveness in those who have vasovagal syncope may be reversed by blocking nitric oxide synthase. Thus, they sought to evaluate volunteers who either had vasovagal syncope or were otherwise healthy, what the effect of a nitric oxide synthase inhibitor would be. They demonstrated that arterial vasoconstriction is impaired in young vasovagal syncope patients but inhibiting nitric oxide synthase could correct this problem. Namely, that this might provide a potential mechanism of avoiding the changes in blood pressure associated with orthostatic intolerance resulting in vasovagal syncope. Whether or not this proves to be an ambulatory therapy still remains to be seen but at least in the acute study state within which these patients were evaluated, it suggests to be a potential promising target. The next paper we review is also published in Heart this past month by Lazzerini et al., entitled Systemic inflammation as a novel QT-prolonging risk factor in patients with torsades de pointes. There is increasing evidence of the role systemic inflammation can play in arrhythmogenesis and particularly in acquired long QT syndrome in patients with sarcoid or myocarditis and other disease states is well recognized that ventricular arrhythmias that are potentially life threatening can happen. What the role of correcting this inflammatory state is, is less clear. However, this group decided to evaluate whether systemic inflammation may represent a currently overlooked risk factor contributing to torsades de pointes in the general population. They looked at 40 consecutive patients who experienced torsades and enrolled them to evaluate circulating levels of different inflammatory biomarkers and compared them with patients with active rheumatoid arthritis, comorbidity or healthy controls. They demonstrated that in the torsades group, 80% of patients showed an elevated inflammatory markers and in fact a definite inflammatory disease was identifiable in 18 of the 40 patients with 12 having acute infections, five having immune mediated diseases and one described as other. Thus they proposed that systemic inflammation via elevated IL-6 levels could represent a novel QT-prolonging risk factor that can contribute to torsades. In their group they showed that CRP reduction was associated with IL-6 level decrease and resulted in QTC shortening. It remains to be seen whether this increased inflammatory pathway might be due to the torsades event itself or the cause. However, it does bring up the interesting question of whether or not systemic inflammation may in fact be causing untoward effects on normal arrhythmic profiles resulting in a greater risk of ventricular arrhythmias. The next article we review is published by Kottkamp et al., entitled Global multielectrode contact mapping plus ablation with a single catheter: Preclinical and preliminary experience in humans with atrial fibrillation in this past month's issue of the Journal of Cardiovascular Electrophysiology. Within the realm of catheter ablation for atrial fibrillation, There's a constant search for new approaches to achieve either more durable or quicker or safer pulmonary vein isolation. It is well recognized that pulmonary vein isolation is the cornerstone of atrial fibrillation ablation. In this particular paper, they sought to evaluate the utility of a catheter, namely a basket catheter that could allow for both diagnostic mapping as well as targeted ablation. This novel catheter has a distal multielectrode array with 16 ribs with 122 gold-plated electrodes. With each electrode being able to ablate, pace and able to measure tissue contact, temperature, current, and intracardiac electrograms. They noted in three patients that complete pulmonary vein isolation was achieved in all 12 and in most veins, PVI was achieved with a single placement in front of that respective vein though in one case there was a single gap requiring reapplication. This suggests a new technique for quote unquote, single shot pulmonary vein isolation. Furthermore, the fact that multiple electrodes could be used to map at the same time as performing ablation, suggest that there might be opportunities for mapping more than just the veins themselves. What the safety and utility of this approach would be over other quote unquote, single shot approaches, such as laser and cryo based balloon systems, is unclear. Furthermore, whether or not they actually reflect a paradigm that offer additional utility due to the ability for more mapping, also remains to be seen. However, the critical portion of understanding these different tools is being able to differentiate them in practice and understanding what their relative values and opportunities are will be critical as one makes selections of which technologies to use. The next article we review is published in Europace this past month by Hellenthal et al., entitled Molecular autopsy of sudden unexplained deaths reveals genetic predispositions for cardiac diseases among young forensic cases. While we recognize that coronary artery disease causes the majority of sudden cardiac deaths in the older population. When we have a young patient who experiences sudden cardiac death, we always have to be concerned about the role of a genetic component. This is not just important for the patient themselves but also for family members who might still be alive. In this study they sought to determine the portion of underlying genetic heart disease among unexplained putative sudden cardiac death cases from a large German forensic departments. The number included were only 10 patients who had sudden unexplained death aged 19 to 40 years. DNA was analyzed for 174 candidate genes and also genetic testing was offered to affected families. Amongst 172 forensic cases again, 10 cases of sudden unexplained death were identified and a genetic disposition was found in eight of 10 cases, with pathogenic mutations in three and variants of uncertain significance in five. Furthermore, subsequent selective screening of the family members revealed two additional mutation carriers in family members who had not suffered from a sudden death event yet. The role of molecular autopsy in patients is evolving. However, the amount of molecular autopsies that are sent are still too low. All patients who are young and die unexpectedly, might benefit from molecular autopsy beyond just traditional forensic pathology to understand whether or not there's a genetic predisposition that led to their event. This might help the family members of that affected individual, especially in understanding whether or not they may also be at risk. The next article we review is by Constantino et al., entitled Neural networks as a tool to predict syncope risk in the Emergency Department in Europace this past month. Many patients when they pass out immediately come into the emergency department. However, it can be very difficult to understand what the risk of that syncope patient is and thus many are automatically admitted to the hospital despite the fact that history might provide a lot of data. In this study, Constantino et al., sought to evaluate the utility for artificial neural networks in stratifying risk in patients presenting with syncope to the hospital. They analyzed individual level data from three prior prospective studies and included a a cumulative sample of 1,844 patients. They included ten variables from patient history, ECG, and the circumstances of syncope to train and test the neural network. They actually had two different approaches used for training and validating neural network given the exploratory nature of the study. They found that they could identify adverse events after syncope with a sensitivity if 95% if they used one approach versus 100% if they used an approach that considers more factors. Thus the study suggested that artificial neural networks could effectively predict the short-term risk of patients with syncope after presenting to the emergency departments. They did not seek to address what the predictive capability of the artificial neural network would be when compared with traditional clinical judgment and existing rule sets that might exist in various emergency departments. The reason this study's important is that as artificial neural networks become more robust we might find that their role in complementing physician decision making might become more and more important. This is especially true on the front lines amongst emergency department physicians or in other groups and consideration of employment of novel technologies or rule sets or methodologies to augment decision making on risk of patients who are being evaluated might need to be considered. It also might help individual stratify patients into those that require sooner evaluation. The final article we review is published in the Journal of Interventional Cardiac Electrophysiology this past month by Schmier et al., entitled Effect of battery longevity on costs and health outcomes associated with cardiac implantable electronic devices: a Markov model-based Monte Carlo simulation. Economic effects of increasing utilization of cardiac implantable electronic devices is of increasing concern. We also note that a lot of focus goes on what the battery life of a device is. However, how that battery longevity might affect overall cost and health outcomes is less clear. Thus in this study, Schmier et al., sought to develop a Monte Carlo Markov model simulation model to evaluate what happens to patients based on the battery longevity. They sought evaluations such as infection and non-infectious complication rates as well as overall costs over the lifetime of that individual patient. These outcomes were largely derived from Medicare data. They noted that an increase in battery longevity was an associated reduction in the number of revisions needed by 23%, the number of battery changes needed by 44%, the number of infections by 23%, the number of non-infectious complications by 10% and total costs per patient by 9%. Thus, they demonstrated that using batteries that have longer longevity could be associated with fewer adverse outcomes and reduced healthcare costs. The understanding of the magnitude of the cost benefits of extended battery life is critical and how to optimize the battery life is also critical. It might be that as we move forward, when encountering a situation or a patient in which the battery life is far less than expected, consideration of the reasons why that battery life was limited will be critical in order to optimize the ongoing chronic care of that patient. Both to reduce the burden on the healthcare system and to improve that individual patient's long term outcomes in terms of infectious risk or other issues. This is primarily simulation model and was not necessarily tested in a prospective fashion though this would be quite difficult given the long duration over which would be required to see a lot of these beneficial costs and complication rate effects. However, it is provocative in the fact that it allows us to understand that there might be benefits from taking further care in selecting not just the right device based on indication but the right device based on patient age, the number of general changes one expects a patient to have and what the longevity of that patient is expected to be. I appreciate everyone's attention in these key and hard hitting articles that we have just focused on from this past months of cardiac electrophysiology across the literature. Thanks for listening. Now back to Paul. Paul Wang: Thanks Suraj. You did a terrific job surveying all journals for the latest articles on topics of interest in our field. There's not an easier way to stay in touch with the latest advances. These summaries and a list of all major articles in our field each month can be downloaded from the Circulation, Arrhythmia and Electrophysiology website. We hope you'll find the journal to be the go to place for everyone interested in the field. See you next month.
Rank #1: VT/VF after MI. Commentary by Dr. David Wilber
Rank #2: Thromboembolism within 30 Days of Electrical Cardioversion in Acute Onset Atrial Fibrillation. Commentary by Dr. David Wilber